rs3810741

Variant names:

• chrX-9765909-C-T
• rs3810741
• ENST00000929112.1:c.-92G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000929112.1(GPR143):​c.-92G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 878,720 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 37 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., 9 hem., cov: 24)
  • Exomes 𝑓: 0.00010 (0 hom. 28 hem.)
• Consequence: GPR143 ENST00000929112.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.894
• Publications: 3 publications found

Genes affected

GPR143 (HGNC:20145): (G protein-coupled receptor 143) This gene encodes a protein that binds to heterotrimeric G proteins and is targeted to melanosomes in pigment cells. This protein is thought to be involved in intracellular signal transduction mechanisms. Mutations in this gene cause ocular albinism type 1, also referred to as Nettleship-Falls type ocular albinism, a severe visual disorder. A related pseudogene has been identified on chromosome Y. [provided by RefSeq, Dec 2009]

GPR143 Gene-Disease associations (from GenCC):

• GPR143-related foveal hypoplasia

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• ocular albinism

  Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
• nystagmus 6, congenital, X-linked

  Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• X-linked recessive ocular albinism

  Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000249 (28/112397) while in subpopulation EAS AF = 0.00661 (23/3479). AF 95% confidence interval is 0.00452. There are 0 homozygotes in GnomAd4. There are 9 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 9 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000929112.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR143	NM_000273.3	MANE Select	c.-92G>A		upstream_gene	N/A	NP_000264.2	P51810
	GPR143	NM_001440781.1		c.-92G>A		upstream_gene	N/A	NP_001427710.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR143	ENST00000929112.1		c.-92G>A		5_prime_UTR	Exon 1 of 8	ENSP00000599171.1
	GPR143	ENST00000447366.5	TSL:3	c.-2-5083G>A		intron	N/A	ENSP00000390546.2	H7BZN6
	GPR143	ENST00000431126.1	TSL:3	c.-3+211G>A		intron	N/A	ENSP00000406138.1	C9J9N1

Frequencies

GnomAD3 genomes AF: 0.000249 AC: 28 AN: 112349 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000933

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00659

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00113 AC: 4 AN: 3529 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0180

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000102 AC: 78 AN: 766323 Hom.: 0 Cov.: 12 AF XY: 0.000151 AC XY: 28 AN XY: 185819

African (AFR) AF: 0.000547 AC: 9 AN: 16440

American (AMR) AF: 0.000127 AC: 1 AN: 7892

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10417

East Asian (EAS) AF: 0.00300 AC: 58 AN: 19328

South Asian (SAS) AF: 0.0000940 AC: 2 AN: 21274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2134

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 636414

Other (OTH) AF: 0.000248 AC: 8 AN: 32272

GnomAD4 genome AF: 0.000249 AC: 28 AN: 112397 Hom.: 0 Cov.: 24 AF XY: 0.000260 AC XY: 9 AN XY: 34569

African (AFR) AF: 0.000129 AC: 4 AN: 31096

American (AMR) AF: 0.0000932 AC: 1 AN: 10729

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2653

East Asian (EAS) AF: 0.00661 AC: 23 AN: 3479

South Asian (SAS) AF: 0.00 AC: 0 AN: 2706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53114

Other (OTH) AF: 0.00 AC: 0 AN: 1540

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000495

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.90
PhyloP100		0.89
PromoterAI		0.098	Neutral
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3810741; hg19: chrX-9733949;